The general aim of this research program is to continue our studies utilizing centrally, peripherally and reflex evoked electrodermal responses (EDR) as a model for investigating the effects of drugs on the central nervous system (CNS). As the peripheral neurotransmitter to the sweat glands is acetylcholine, this system appears to be particularly suitable for the study of those adrenergic drugs thought to have a central action in addition to their known peripheral effects. Studies will be directed toward investigation of the effects of a variety of "sympatho-inhibitory" agents on centrally and peripherally evoked EDRs with the goal of not only determining whether or not they exhibit a CNS action but also to investigate the central site(s) of action. This will be accomplished by simultaneously studying the effects of these agents with regard to central control of the pupil and whether or not they have the same quantitative effect on the central nervous system, on both of these autonomic systems, in the presence of central alpha-blockers such as yohimbine hydrochloride. Particular emphasis will be directed towards investigating effects at the level of the spinal cord. Electrodermal reflexes can be elicited in intact, decerebrate and spinal preparations. Preliminary observation suggest that the lower brain stem exerts tonic inhibitory influences descending to spinal levels which may be selectively antagonized by yohimbine. The remaining proposed studies focus on characterization of the physiology of EDR reflex mechanisms with particular attention to the above mentioned inhibitory tone. Pharmacological studies will be directed toward understanding the central effects and interactions of clonidine, chlorpromazine and yohimbine on several autonomic systems (EDR, pupil and nictitating membrane). The use of the information obtained from these studies might then provide us with the unique opportunity to more specifically delineate the neurotransmitter mechanisms involved with regard to this particular autonomic system.